- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05280405
Early Proactive Therapeutic Drug Monitoring of Infliximab in Children: EPIC Study (EPIC)
Impact of Early Proactive Therapeutic Drug Monitoring on the Durability and Efficacy of Infliximab Therapy in Pediatric Inflammatory Bowel Disease: a Multicenter Open-label Randomized-control Trial
Study Overview
Detailed Description
Inflammatory Bowel Disease (IBD) are relapsing disorders with progressive bowel damage leading to long-term disability.
Infliximab (IFX), is a highly effective and commonly used biologic in IBD. However, up to 40% of patients do not respond to treatment or lose response over time. Low-serum IFX concentrations and the development of antibodies to IFX (ATI) are two major factors affecting IFX efficacy, durability and safety. Standard IFX dose is administered as an IV (in the vein) infusion at 5 mg/kg in a 0, 2, and 6 weeks induction regimen followed by a maintenance regimen with infusions every 8 weeks. This standard dosing is extrapolated from adult studies. IFX has a highly variable pharmacokinetic and pharmacodynamics that is dependent on body weight, disease extent, levels of inflammation and the presence of ATI. In children and young adults with IBD all these factors often result in low-serum IFX concentrations.
Proactive therapeutic drug monitoring, consists in the measurement of drug concentrations on patient's blood, in order to adjust the following administrations (dosing or interval) and maintain a desired concentration of the medication in the body.
This study seeks to determine whether a proactive therapeutic drug monitoring strategy can improve IFX durability, efficacy and safety in children and young adults with IBD. The study will involve approximately 90 patients, aged 6 to 17 years, with IBD. All the patients enrolled in the study will receive IFX at 5mg/kg at week 0, 2 and 6. At week 6 patients will be randomly assigned to receive IFX treatment either based on IFX concentrations determined before every IFX infusion (intervention group) or at standard dosing (control group). Patients will participate in the study for 54 weeks (approximately 12 months) or until IFX discontinuation. During the study, patients will visit the study center at the time of every IFX infusion or in case of disease flares.
Study Type
Enrollment (Estimated)
Phase
- Phase 4
Contacts and Locations
Study Contact
- Name: Sara Lega, MD PhD
- Phone Number: +390403785380
- Email: sara.lega@burlo.trieste.it
Study Contact Backup
- Name: Sara Lega
- Phone Number: +390403785380
- Email: sara.lega@burlo.trieste.it
Study Locations
-
-
-
Trieste, Italy, 34137
- Recruiting
- Institute for Maternal and Child Health - IRCCS "Burlo Garofolo"
-
Contact:
- Sara Lega, MD PhD
- Phone Number: 0403785380
- Email: sara.lega@burlo.trieste.it
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Anti-TNF naïve children and adolescents, 6-17 years, with a diagnosis of IBD confirmed by a prior endoscopic biopsy that is consistent with the diagnosis
- Indication to start anti-TNF therapy in accordance with current pediatric guidelines for the treatment of pediatric IBD
- Active inflammation supported by CRP > 5mg/L and /or FC > 150 μg/g before the 1st IFX dose
Exclusion Criteria:
- Consent withdrawal,
- Stenosing or penetrating disease requiring surgery, abdominal abscess, symptomatic stricture,
- Abdominal surgery within the previous 6 months,
- Acute severe ulcerative colitis attack defined by a PUCAI score Ñ 65,
- Infective contraindication to IFX treatment including positive tuberculin skin test or Quantiferon-TB test, recent opportunistic infection, infection with hepatitis B (HBV), C (HCV), human immunodeficiency virus (HIV),
- Previous exposure to anti-TNF;
- Exposure to concomitant prohibited medications including other biologics (including but not limited to ustekinumab, vedolizumab, abatacept, anakinra..), thalidomide, investigational drugs
- Pregnancy or lactation
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Early-Proactive Therapeutic Drug Monitoring (E-pTDM)
Infliximab (IFX) at 5mg/kg, IV at week 0, 2 and 6.
From week 6, the infusion interval will be adjusted based on pre-infusion IFX concentrations to target a trough level grater or equal to (>=) 5 mcg/ml (> 10 μg/ml in patients with perianal disease).
For IFX concentrations below target, the infusion interval will be shortened (minimum interval 2 weeks).
IFX dose increase will be performed as a second step.
|
Infliximab
|
Active Comparator: Standard dosing
Infliximab (IFX) at 5mg/kg, IV at week 0, 2 and 6 followed by 5mg/kg infusions every 8 weeks.
|
Infliximab
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Frequency of IFX discontinuation or need for treatment intensification due to non-response or LOR during the first year of treatment.
Time Frame: 54 weeks
|
Composite outcome.
Treatment intensification is defined as adjunction of rescue therapies, including corticosteroids systemic or topical, azathioprine (AZA), methotrexate (MTX), 5-aminosalicylate (5-ASA) systemic or topical, or rescue IFX escalation or surgery; treatment response is defined as a decrease in Pediatric Crohn's Disease Activity Index (PCDAI) by 12.5 point or in Pediatric Ulcerative Colitis Activity Index (PUCAI) by 10 points with decrease in C reactive protein (CRP) by 50% after induction, evaluated between 12-14 weeks; loss of response (LOR) is defined as PCDAI >= 10 or PUCAI > 10 with CRP > 0.5mg/dl and/or fecal calprotectin (FC) >250 microg/g in a patient who previously responded to induction treatment.
|
54 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Cumulative probability of IFX discontinuation
Time Frame: 54 weeks
|
Time to IFX discontinuation
|
54 weeks
|
Cumulative probability of Loss of Response
Time Frame: 54 weeks
|
Time to Loss of Response (LOR), with LOR defined as PCDAI >= 10 or PUCAI > 10 with CRP > 0.5 mg/dl and/or FC >250 microg/g in a patient who previously responded to induction treatment.
|
54 weeks
|
Frequency of subtherapeutic IFX concentrations
Time Frame: 54 weeks
|
Subtherapeutic IFX concentration is defined as IFX concentration at trough < 5 microg/ml (or <10 microg/ml in perianal CD) during maintenance treatment.
|
54 weeks
|
Frequency of Anti-Infliximab Antibodies
Time Frame: 54 weeks
|
Evaluation of Anti-Infliximab Antibodies
|
54 weeks
|
Frequency of infusion reactions
Time Frame: 54 weeks
|
Infusion reactions are defined as reactions that develop during the course of the infusion or within 1-2h of its completion.
|
54 weeks
|
Frequency of endoscopic remission
Time Frame: 54 weeks
|
Endoscopic remission is defined in patients with Crohn's Disease as a Simple Endoscopic score for Crohn's Disease (SES-CD score) less than or equal to (<=) 2 and in patients with Ulcerative Colitis as a Mayo sub-score <= 1
|
54 weeks
|
Frequency of patients with treatment response at the end of induction between 12 and 14 weeks
Time Frame: Week 14
|
Treatment response is defined as a decrease in PCDAI by 12.5 point or in PUCAI by 10 points with decrease in CRP by 50% compared to baseline
|
Week 14
|
Frequency of patients with clinical remission at 14 weeks
Time Frame: Week 14
|
Clinical remission is defined as PCDAI <10 or PUCAI <10
|
Week 14
|
Frequency of clinical and biochemical remission at week 14
Time Frame: Week 14
|
Clinical and Biochemical remission is defined as PCDAI <10 or PUCAI <10 with CRP < 0.5 mg/dl and FC < 250 microg/g
|
Week 14
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2021-003220-32
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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